tbuckley/cabot-search huggingface dataset:
LTBK-03. Targeted mass spectrometry of serial CSF and serum specimens from children with diffuse intrinsic pontine glioma treated with intracranial B7-H3 CAR T cells
Authors: Nicholas Vitanza, Ashley Wilson, Wenjun Huang, Jeffrey Whiteaker, Juliane Gust, Rimas Orentas, Rebecca Gardner, Julie Park, Michael Jensen, Amanda Paulovich
Journal: Neuro-Oncology (2022)

Abstract Considering the high expression of B7-H3 (CD276) on diffuse intrinsic pontine glioma (DIPG) and preliminary evidence that repeated locoregional delivery of CAR T cells to patients with CNS tumors was feasible and tolerable, we open the phase 1 trial BrainChild-03 (NCT04185038). Children with DIPG in Dose Regimen 1 received 40 intraventricular B7H3CAR doses, with the two patients enrolling post-progression surviving &amp;gt;400 days from initial CAR T infusion. To evaluate for immune and tumor responses that may correlate with clinical and radiographic evaluations, we performed targeted proteomic analysis on serial CSF and serum biospecimens. MRM-MS is a targeted mass spectrometry that provides sensitive measurement of proteins in cancer tissues and fluids. In 2 patients with longitudinal biospecimens, we identified 50 CSF and 59 serum proteins above level of detection. In general, there were fewer serum fluctuations compared to the CSF, supporting that intracranial delivery provides local immune activation. Sharp fluctuations of several immunoregulatory peptides were measured in the CSF at pre and post infusion timepoints, including BCL10, CXCL13, TIM-3, ICOSLG, and PD-L2. Notably, several analytes tracked consistently in the CSF of both patients, including markers of macrophage maturation and immune cell recruitment, including CD14, CD163, CD44, CSF-1, CXCL13 and VCAM-1. B7-H3 was detected in the CSF and serum of both patients. S005, who progressed on protocol therapy, had a sharp increase in B7-H3 in the CSF during Course 2, while S008, who had clinical improvement on protocol therapy, had consistently lower B7-H3 present. Notably, serum B7-H3 steadily declined in both patients over time, with the exception of a transient increase in S005 between Courses 4 and 5. Future work for all enrolled patients with DIPG will explore the correlation of these targeted proteomic measurements with clinical end points for potential use as markers of efficacy of therapy or adverse events.
Suprasellar Hemangioblastoma on 68Ga-DOTATATE PET/CT
Authors: Nuh Filizoglu, Salih Ozguven
Journal: Clinical Nuclear Medicine (2022)

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome that is characterized by the presence of various malignant and benign tumors, including retinal and central nervous system hemangioblastomas. Hemangioblastomas are highly vascular tumors that can occur sporadically or within VHL disease. Herein, we present 68 Ga-DOTATATE PET/CT findings of a unique case of suprasellar hemangioblastoma in a 52-year-old man with VHL disease.
Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells
Authors: Peng Wang, Esra Karakose, Carmen Argmann, Huan Wang, Metodi Balev, Rachel I. Brody, Hembly G. Rivas, Xinyue Liu, Olivia Wood, Hongtao Liu, Lauryn Choleva, Dan Hasson, Emily Bernstein, Joao A. Paulo, Donald K. Scott, Luca Lambertini, James A. DeCaprio, Andrew F. Stewart
Journal: Journal of Clinical Investigation (2022)

Resistance to regeneration of insulin-producing pancreatic β cells is a fundamental challenge for type 1 and type 2 diabetes. Recently, small molecule inhibitors of the kinase DYRK1A have proven effective in inducing adult human β cells to proliferate, but their detailed mechanism of action is incompletely understood. We interrogated our human insulinoma and β cell transcriptomic databases seeking to understand why β cells in insulinomas proliferate, while normal β cells do not. This search reveals the DREAM complex as a central regulator of quiescence in human β cells. The DREAM complex consists of a module of transcriptionally repressive proteins that assemble in response to DYRK1A kinase activity, thereby inducing and maintaining cellular quiescence. In the absence of DYRK1A, DREAM subunits reassemble into the pro-proliferative MMB complex. Here, we demonstrate that small molecule DYRK1A inhibitors induce human β cells to replicate by converting the repressive DREAM complex to its pro-proliferative MMB conformation.
Reference Values for Dopamine Transporter Imaging With 99mTc-TRODAT-1 in Healthy Subjects and Parkinson’s Disease Patients
Authors: Felipe Arriva Pitella, Ana Carolina Trevisan, Leonardo Alexandre-Santos, Mery Kato, Manuelina Mariana Capellari Macruz Brito, Vitor Tumas, Lauro Wichert-Ana
Journal: Clinical Nuclear Medicine (2022)

The aim of this study was to evaluate different quantitative indexes of striatum dopamine transporter density in healthy subjects and patients with PD.Sixty-seven patients, 23 healthy (8 male; 59 ± 11 years old) and 44 age-matched patients (29 male; 59 ± 7 years old), with various degrees of severity of idiopathic PD (duration of symptoms, 10 ± 6 years; Hoehn and Yahr Scale, 2.16 ± 0.65; UPDRS-3, 29.74 ± 17.79). All patients performed 99m Tc-TRODAT-1 SPECT. Binding potential indexes (BPIs) of striatum and subregions, asymmetry index (AI), and putamen/caudate ratio (P/C) were calculated.Binding potential index was lower in the PD than in healthy subjects. A BPI cutoff for striatum and putamen ranging from 0.73 to 0.78 showed 95% to 100% sensitivity and 84% to 88% specificity. For the caudate nucleus, a BPI threshold of 0.8 to 0.88 revealed 100% sensitivity and 77% to 84% specificity. The BPI's respective areas under the curve ranged from 0.92 to 0.98. For AI and P/C, the area under the curve was less than 0.70. Binding potential index intraclass correlation coefficient was close to 1.0 in the intraobserver evaluation and 0.76 to 0.87 in the interobserver assessment. Intraclass correlation coefficient for AI and P/C was inferior to 0.75 in the intraobserver and interobserver evaluations.Different semiquantitative indices differentiated PD and healthy subjects and may help the differential diagnosis of other entities involving the dopaminergic system. Asymmetry index and P/C performances were lower than BPI, including their intraobserver and interobserver reliability, and therefore should be used with caution.
Seasonality of influenza and coseasonality with avian influenza in Bangladesh, 2010–19: a retrospective, time-series analysis
Authors: Isha Berry, Mahbubur Rahman, Meerjady Sabrina Flora, Tahmina Shirin, A S M Alamgir, Manjur Hossain Khan, Rubaid Anwar, Mona Lisa, Fahmida Chowdhury, Md Ariful Islam, Muzzafar G Osmani, Stacie Dunkle, Eric Brum, Amy L Greer, Shaun K Morris, Punam Mangtani, David N Fisman
Journal: The Lancet Global Health (2022)

Seasonal and avian influenza viruses circulate among human and poultry populations in Bangladesh. However, the epidemiology of influenza is not well defined in this setting. We aimed to characterise influenza seasonality, examine regional heterogeneity in transmission, and evaluate coseasonality between circulating influenza viruses in Bangladesh.
Striving for zero hunger in an uncertain world
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2022)

In the summer of 2010, a drought and associated heatwave afflicted western Russia, reducing Russian wheat yields by about a third, spooking international markets and raising the price of grain. In response to these price rises, and in the hope of protecting local consumers and livestock farmers, the Russian government banned grain exports, pushing international grain prices even higher. The resultant higher cost of bread and flour around the world exacerbated poverty and food insecurity in many countries and may have contributed to the unrest of the "Arab Spring", while export bans did little to protect Russians from higher food prices.
Risk factors for apathy in Alzheimer’s disease: A systematic review of longitudinal evidence
Authors: Ignacia Azocar, Penny Rapaport, Alexandra Burton, Georgia Meisel, Vasiliki Orgeta
Journal: Ageing Research Reviews (2022)

Apathy is frequent and persistent in Alzheimer's disease (AD), associated with poor prognosis and carer distress; yet our knowledge of risk factors remains limited.To identify risk factors associated with apathy incidence and progression in AD over time.We systematically reviewed evidence based on longitudinal studies assessing risk factors for apathy in AD up to June 2021. Two authors independently assessed article eligibility and rated quality.13,280 articles were screened, of which 13 met inclusion criteria. Studies had a mean follow-up of 2.7 years reporting on a total of 2012 participants. Most findings were based on single studies of moderate quality evidence. Risk factors increasing apathy onset were: being a carrier of the T allele of the PRND gene polymorphism, and having high levels of the IL-6 and TNFα cytokines at baseline. Risk factors for apathy worsening were: reduced inferior-temporal cortical thickness, taking antidepressants, being an ApoE ε4 carrier, living longer with AD, lower cognitive test scores, higher baseline apathy, premorbid personality traits (lower agreeableness, higher neuroticism), and higher midlife motivational abilities.Although results are limited by the small number of studies, this review identified specific genetic, neurobiological, AD specific, and dispositional factors that may increase risk of apathy onset and worsening in AD.
Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial
Authors: Sean R Bennett, James M McCarty, Roshan Ramanathan, Jason Mendy, Jason S Richardson, Jonathan Smith, Jeff Alexander, Julie E Ledgerwood, Paul-André de Lame, Sarah Royalty Tredo, Kelly L Warfield, Lisa Bedell
Journal: The Lancet Infectious Diseases (2022)
Correction: GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer
Authors: Grainne M. O'Kane, Barbara T. Grünwald, Gun-Ho Jang, Mehdi Masoomian, Sarah Picardo, Robert C. Grant, Robert E. Denroche, Amy Zhang, Yifan Wang, Jessica K. Miller, Bernard Lam, Paul M. Krzyzanowski, Ilinca M. Lungu, John M.S. Bartlett, Melanie Peralta, Foram Vyas, Rama Khokha, James Biagi, Dianne Chadwick, Stephanie Ramotar, Shawn Hutchinson, Anna Dodd, Julie M. Wilson, Faiyaz Notta, George Zogopoulos, Steven Gallinger, Jennifer J. Knox, Sandra E. Fischer
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), author Jessica K. Miller is mistakenly omitted from the author list. In addition, the name of author Ilinca M. Lungu is incorrect. The errors have been corrected in the latest online HTML and PDF versions of the article and the author contributions and disclosures have been updated as necessary. The authors regret the errors.
Watching Parkinson’s disease with wrist-based sensors
Authors: James A. Diao, Marium M. Raza, Kaushik P. Venkatesh, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

Parkinson's disease (PD) lacks sensitive, objective, and reliable measures for disease progression and response. This presents a challenge for clinical trials given the multifaceted and fluctuating nature of PD symptoms. Innovations in digital health and wearable sensors promise to more precisely measure aspects of patient function and well-being. Beyond research trials, digital biomarkers and clinical outcome assessments may someday support clinician-initiated or closed-loop treatment adjustments. A recent study from Verily Life Sciences presents results for a smartwatch-based motor exam intended to accelerate the development and evaluation of therapies for PD.
Unexplained Acute Pediatric Hepatitis Cases Worldwide
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
COVID-19 Treatments for Nonhospitalized Patients—Reply
Authors: Rajesh T. Gandhi, Preeti N. Malani, Carlos del Rio
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<i>Clostridium difficile</i> infection risk in patients with hidradenitis suppurativa
Authors: Anuj Pranav Sanghvi, J. Alex Miles, Christopher Sayed
Journal: British Journal of Dermatology (2022)

Widespread use of antibiotics for hidradenitis suppurativa (HS) opens up the possibility of Clostridium difficile infection (CDI) and an increased risk of mortality. The purpose of this study was to identify risk factors for acquiring CDI in patients with HS. We suggest that providers should take risk factors including increased antibiotic class, hospitalizations, and advanced patient age into consideration when prescribing antibiotics for HS.
Unexpected sudden rise of human monkeypox cases in multiple non-endemic countries amid COVID-19 pandemic and salient counteracting strategies: Another potential global threat?
Authors: Ranjan K. Mohapatra, Hardeep Singh Tuli, Ashish K. Sarangi, Sandip Chakraborty, Deepak Chandran, Chiranjib Chakraborty, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
Long-Term Impairments Are Most Pronounced in Critically Ill Patients with COVID-19 with Severe Obesity
Authors: Emma Kooistra, Hidde Heesakkers, Peter Pickkers, Marieke Zegers, Mark van den Boogaard
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

To the Editor:Although obesity is an important risk factor for the development of severe coronavirus disease (COVID-19) (1), once admitted to the ICU, no clear relationship between body mass index (BMI) and short-term outcomes is present (2).Many patients experience long-term symptoms after an ICU admission with COVID-19 (3, 4), but it is unknown whether the prevalence rates of long-term symptoms differ between different BMI groups.Therefore, this study aimed to examine the differences between BMI categories in the occurrence of physical, mental, and cognitive symptoms 3 and 12 months after ICU treatment in critically ill patients with COVID-19. MethodsIn this prospective multicenter cohort study, patients with COVID-19 admitted to ICUs in 11 Dutch hospitals between March 1, 2020 and July 1, 2020 were included after obtaining informed consent (5).Patients received three questionnaires regarding their health status: pre-ICU (baseline; answered in retrospect as soon possible after ICU admission), and 3 and 12 months after ICU treatment, which could be completed by the patient or a proxy.Patients who completed the baseline and 12-month follow-up questionnaires without missing data on BMI were included in the analyses.Four hospitals were not able to provide 3-month data.Primary outcomes were occurrence of physical (fatigue and new physical problems), mental (symptoms of
Human midbrain dopaminergic neuronal differentiation markers predict cell therapy outcomes in a Parkinson’s disease model
Authors: Peibo Xu, Hui He, Qinqin Gao, Yingying Zhou, Ziyan Wu, Xiao Zhang, Linyu Sun, Gang Hu, Qian Guan, Zhiwen You, Xinyue Zhang, Wenping Zheng, Man Xiong, Yuejun Chen
Journal: Journal of Clinical Investigation (2022)

Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.
Potential Pitfall in the Interpretation of Ganglioneuronal Uptake of 18F-PSMA-1007 PET/CT Scans Performed With a High Spatial Resolution Digital PET Scanner
Authors: Nadya Kisiel, Paul Thomas
Journal: Clinical Nuclear Medicine (2022)

A 69-year-old man with biochemical recurrence of prostate cancer after radical prostatectomy 5 years previously and subsequent salvage radiotherapy to the prostate bed and pelvic nodes underwent PET/CT on a Siemens mCT Flow PET and a second PET/CT 10 months later on a Siemens Vision 600 Digital PET. In addition to a suspicious left hilar lymph node, the new high-resolution PET showed increased visualization and avidity of physiologic uptake in paraspinal and presacral sympathetic ganglia. Caution should be undertaken when interpreting PET/CTs performed on high-resolution digital scanners to avoid mistaking ganglia uptake for metastatic disease.
Genomic profiling identifies distinct genetic subtypes in extra-nodal natural killer/T-cell lymphoma
Authors: Gehong Dong, Xuxiang Liu, Lifu Wang, Wenjuan Yin, Alyssa Bouska, Qiang Gong, Kunal Shetty, Lu Chen, Sunandini Sharma, Jibin Zhang, Carmen Lome-Maldonado, Leticia Quintanilla-Martinez, Yuping Li, Joo Y. Song, Wenyan Zhang, Yunfei Shi, Jinhui Wang, Lingbo Kong, Xiwei Wu, Jingwen Wang, Hong-gang Liu, Lingfei Kong, Wenyong Sun, Weiping Liu, Lili Wang, Timothy W. McKeithan, Javeed Iqbal, Wing C. Chan
Journal: Leukemia (2022)
Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations
Authors: Kai Wang, Xian Shi, Ziwei Zhu, Xingjie Hao, Liangkai Chen, Shanshan Cheng, Roger S. Y. Foo, Chaolong Wang
Journal: Genome Medicine (2022)

Abstract Background Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite enormous efforts devoted to its prevention and treatment. While many genetic loci have been identified to associate with CAD, the intermediate causal risk factors and etiology have not been fully understood. This study assesses the causal effects of 37 heritable clinical factors on CAD in East Asian and European populations. Methods We collected genome-wide association summary statistics of 37 clinical factors from the Biobank Japan (42,793 to 191,764 participants) and the UK Biobank (314,658 to 442,817 participants), paired with summary statistics of CAD from East Asians (29,319 cases and 183,134 controls) and Europeans (91,753 cases and 311,344 controls). These clinical factors covered 12 cardiometabolic traits, 13 hematological indices, 7 hepatological and 3 renal function indices, and 2 serum electrolyte indices. We performed univariable and multivariable Mendelian randomization (MR) analyses in East Asians and Europeans separately, followed by meta-analysis. Results Univariable MR analyses identified reliable causal evidence ( P &lt; 0.05/37) of 10 cardiometabolic traits (height, body mass index [BMI], blood pressure, glycemic and lipid traits) and 4 other clinical factors related to red blood cells (red blood cell count [RBC], hemoglobin, hematocrit) and uric acid (UA). Interestingly, while generally consistent, we identified population heterogeneity in the causal effects of BMI and UA, with higher effect sizes in East Asians than those in Europeans. After adjusting for cardiometabolic factors in multivariable MR analysis, red blood cell traits (RBC, meta-analysis odds ratio 1.07 per standard deviation increase, 95% confidence interval 1.02–1.13; hemoglobin, 1.10, 1.03–1.16; hematocrit, 1.10, 1.04–1.17) remained significant ( P &lt; 0.05), while UA showed an independent causal effect in East Asians only (1.12, 1.06–1.19, P = 3.26×10 −5 ). Conclusions We confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD.
Prevention and Initial Management of HIV Infection
Authors: Judith Feinberg, Susana Keeshin
Journal: Annals of Internal Medicine (2022)

Since July 2017, when In the Clinic last addressed management of HIV infection, there have been meaningful improvements in our ability to prevent HIV and to manage patients living with HIV. New approaches to preexposure prophylaxis and more effective treatments have made the elimination of HIV infection a feasible goal. The federal "Ending the HIV Epidemic" initiative aims at a 90% reduction in new HIV diagnoses by 2030. This article provides updated information on how clinicians should use these improvements to manage their patients who are at risk for HIV infection or are newly diagnosed with HIV.